Summary Current organoid technologies require intensive manual manipulation and lack uniformity in organoid size and cell composition. We present here an automated organoid platform that generates uniform organoid precursors in high-throughput. This is achieved by templating from monodisperse Matrigel droplets and sequentially delivering them into wells using a synchronized microfluidic droplet printer. Each droplet encapsulates a certain number of cells (e.g., 1,500 cells), which statistically represent the heterogeneous cell population in a tumor section. The system produces >400-μm organoids within 1 week with both inter-organoid homogeneity and inter-patient heterogeneity. This enables automated organoid printing to obtain one organoid per well. The organoids recapitulate 97% gene mutations in the parental tumor and reflect the patient-to-patient variation in drug response and sensitivity, from which we obtained more than 80% accuracy among the 21 patients investigated. This organoid platform is anticipated to fulfill the personalized medicine goal of 1-week high-throughput screening for cancer patients.

Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that have demonstrated great potential in drug evaluation for personalized medicine. Here, we used a perfusable vascularized tumor spheroid-on-a-chip to simulate the tumor microenvironment in vivo and demonstrated that the PHD inhibitor dimethylallyl glycine prevents the degradation of normal blood vessels while enhancing the efficacy of the anticancer drugs paclitaxel and cisplatin in human esophageal carcinoma (Eca-109) spheroids. Our results point to the potential of this model to evaluate anticancer drugs under more physiologically relevant conditions.

Transplantation of mesenchymal stem cells (MSCs) holds promise to repair severe traumatic injuries. However, current transplantation practices limit the potential of this technique, either by losing the viable MSCs or reducing the performance of resident MSCs. Herein, we design a “bead-jet” printer, specialized for high-throughput intra-operative formulation and printing of MSCs-laden Matrigel beads. We show that high-density encapsulation of MSCs in Matrigel beads is able to augment MSC function, increasing MSC proliferation, migration, and extracellular vesicle production, compared with low-density bead or high-density bulk encapsulation of the equivalent number of MSCs. We find that the high-density MSCs-laden beads in sparse patterns demonstrate significantly improved therapeutic performance, by regenerating skeletal muscles approaching native-like cell density with reduced fibrosis, and regenerating skin with hair follicle growth and increased dermis thickness. MSC proliferation within 1-week post-transplantation and differentiation at 3 − 4 weeks post-transplantation are suggested to contribute therapy augmentation. We expect this “bead-jet” printing system to strengthen the potential of MSC transplantation.

Endometrial injury and intrauterine adhesions are increasingly reported in recent years; however, treatment options remain limited. Intravenous injection of mesenchymal stem cells (MSCs) for endometrium regeneration has limited effectiveness as the retention rate of transplanted cells is low. Hydrogel‐based tissue‐engineered solutions, such as MSC‐seeded bioscaffolds, are reported to increase retention rates; however, a less invasive alternative is still desirable. 560‐µm homogeneous Matrigel microspheres are fabricated, loading them with about 1500 MSCs and injecting them into the injured endometria of rats’ uteri. This minimally invasive procedure is proved to significantly increase endometrium thickness by over onefold after 21 d (p < 0.0001) and fertility rates from 25% to 75% in impaired and repaired uteri (p < 0.001), respectively. This study provides a minimally invasive alternative to endometrium repair with the promise to establish a broad‐spectrum technique for MSC transplantation.

In microextrusion-based 3D bioprinting, shaping gel fibers online, i.e., in narrow tubes, benefits the structural maintenance after extrusion, but it is challenging for materials possessing slow sol-gel transition dynamics. Gelatin, for example, transforms into thermostable fibers via transglutaminase (TG) reaction in as much as 10 min. It causes dramatic flow resistance accumulation and shear stress increase in fluids moving along narrow tubes, resulting in channel clogging and cell detriments. In this study, we overcome the limitations by adopting cascade pumping and performing in a single peristaltic pump that comprises multi-channel pumping units. The pressure and shear stress reduction by over 1-fold are verified by finite element simulation; continuous gelatin fiber production and patterning in a substrate-free manner are achieved via slow online enzymatic cross-linking. The online fiber shaping can be scaled up by numbering up the pumping units and provides another paradigm for biomanufacturing.

Metrics & MoreArticle Recommendations S ome of the grant numbers for the National Natural Science Foundation of China and the Shenzhen Science and Technology Innovation Commission listed in the Acknowledgements were incorrect.The correct Acknowledgments should read as follows.

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